Since its introduction in the early 1990's, optical coherence tomography (OCT) has emerged as a promising imaging modality for micrometer-scale noninvasive imaging in biological and biomedical applications. Its relatively low cost and real-time, in vivo capabilities have fueled the investigation of this technique for applications in retinal and anterior segment imaging in ophthalmology (e.g., to detect retinal pathologies), early cancer detection and staging in the skin, gastrointestinal, and genitourinary tracts, as well as for ultra-high resolution imaging of entire animals in embryology and developmental biology.
Conventional OCT systems are essentially range-gated low-coherence interferometers that have been configured for characterization of the scattering properties of biological and other samples. By measuring singly backscattered light as a function of depth, OCT fills a valuable niche in imaging of tissue ultrastructure, and provides subsurface imaging with high spatial resolution (˜1-10 μm) in three dimensions and high sensitivity (>110 dB) in vivo with no contact needed between the probe and the tissue. OCT is based on the one-dimensional technique of optical coherence domain reflectometry (OCDR), also called optical low-coherence reflectometry (OLCR). See Youngquist, R. C., S. Carr, and D. E. N. Davies, Optical Coherence Domain Reflectometry: A New Optical Evaluation Technique. Opt. Lett., 1987. 12: p. 158; Takada, K., et al., New measurement system for fault location in optical waveguide devices based on an interferometric technique. Applied Optics, 1987. 26(9): p. 1603-1606; and Danielson, B. L. and C. D. Whittenberg, Guided-wave Reflectometry with Micrometer Resolution. Applied Optics, 1987. 26(14): p. 2836-2842. In some instances of time-domain OCT, depth in the sample is gated by low coherence interferometry. The sample is placed in the sample arm of a Michelson interferometer, and a scanning optical delay line is located in the reference arm.
The time-domain approach used in conventional OCT has been used in supporting biological and medical applications. An alternate approach involves acquiring as a function of optical wavenumber the interferometric signal generated by mixing sample light with reference light at a fixed group delay. Two methods have been developed which employ this Fourier domain (FD) approach. The first is generally referred to as Spectral-domain OCT (SDOCT). SDOCT uses a broadband light source and achieves spectral discrimination with a dispersive spectrometer in the detector arm. The second is generally referred to as swept-source OCT (SSOCT). SSOCT time-encodes wavenumber by rapidly tuning a narrowband source through a broad optical bandwidth. Both of these techniques can provide improvements in SNR of up to 15-20 dB when compared to time-domain OCT, because SDOCT and SSOCT capture the complex reflectivity profile (the magnitude of which is generally referred to as the “A-scan” data or depth-resolved sample reflectivity profile) in parallel. This is in contrast to time-domain OCT, where destructive interference is employed to isolate the interferometric signal from only one depth at a time as the reference delay is scanned.
Surgical visualization has changed drastically since its inception, incorporating larger, more advanced optics toward increasing illumination and field-of-view (FOV). However, the limiting factor in vitreoretinal surgery remains the ability to distinguish between tissues with subtle contrast, and to judge the location of an object relative to other retinal substructures. S. R. Virata, J. A. Kylstra, and H. T. Singh, Retina 19, 287-290 (1999); E. Garcia-Valenzuela, A. Abdelsalam, D. Eliott, M. Pons, R. Iezzi, J. E. Puklin, M. L. McDermott, and G. W. Abrams, Am J Ophthalmol 136, 1062-1066 (2003). Furthermore, increased illumination to supplement poor visualization is also limited by the risks of photochemical toxicity at the retina. S. Charles, Retina 28, 1-4 (2008); J. R. Sparrow, J. Zhou, S. Ben-Shabat, H. Vollmer, Y. Itagaki, and K. Nakanishi, Invest Ophthalmol Vis Sci 43, 1222-1227 (2002). Finally, inherent issues in visualizing thin translucent tissues, in contrast to underlying semitransparent ones, require the use of stains such as indocyanine green, which is toxic to the retinal pigment epithelium. F. Ando, K. Sasano, N. Ohba, H. Hirose, and O. Yasui, Am J Ophthalmol 137, 609-614 (2004); A. K. Kwok, T. Y. Lai, K. S. Yuen, B. S. Tam, and V. W. Wong, Clinical & experimental ophthalmology 31, 470-475 (2003); J. Lochhead, E. Jones, D. Chui, S. Lake, N. Karia, C. K. Patel, and P. Rosen, Eye (London, England) 18, 804-808 (2004).
Spectral domain optical coherence tomography (SDOCT) has demonstrated strong clinical success in retinal imaging, enabling high-resolution, motion-artifact-free cross-sectional imaging and rapid accumulation of volumetric macular datasets. N. A. Nassif, B. Cense, B. H. Park, M. C. Pierce, S. H. Yun, B. E. Bouma, G. J. Tearney, T. C. Chen, and J. F. de Boer, Optics Express 12, 10 (2004); M. Wojtkowski, V. J. Srinivasan, T. H. Ko, J. G. Fujimoto, A. Kowalczyk, and J. S. Duker, Optics Express 12, 2404-2422 (2004). Current generation SDOCT systems achieve <5 μm axial resolutions in tissue, and have been used to obtain high resolution datasets from patients with neovascular AMD, high risk drusen, and geographic atrophy. M. Stopa, B. A. Bower, E. Davies, J. A. Izatt, and C. A. Toth, Retina 28, 298-308 (2008). Other implementations of optical coherence tomography (OCT) including swept-source optical coherence tomography (SSOCT) may offer similar performance advantages.
Preoperative diagnostic imaging using current generation SDOCT systems have demonstrated the ability to provide volumetric datasets of pathologic areas that are otherwise barely visible.